This is an application for a K01 award for Dr. Jeffrey Milush, a post-doctoral fellow at the University of California, San Francisco. Dr. Milush is establishing himself as a young investigator researching the ability of alternative medical interventions to reset neuroendocrine regulation of the immune system. This K01 award will provide Dr. Milush with the support necessary to accomplish the following goals: (1) to become an expert in molecular and flow cytometric analyses of neuroendocrine modulation of immune function; (2) to conduct investigations of the affects of mind-body interventions on immune cell function; (3) to implement biostatistical methods in clinical studies; and (4) to develop the resources necessary for an independent research career. To achieve these goals, Dr. Milush has assembled a mentoring team comprised of a primary mentor, Dr. Douglas Nixon, Associate Chief of the Division of Experimental Medicine, whose laboratory studies immune cell responses to stress and an array of pathogens, and three co-mentors: Dr. Frederick Hecht, Professor of Medicine, Research Director of the UCSF Osher Center for Integrative Medicine, and co-Principal Investigator on the two NCCAM-funded mind-body intervention studies; Dr. Margaret Kemeny, an expert in psychoneuroimmunology and laboratory stress paradigms with experience in clinical trials; and Dr. Peter Bacchetti, an expert in current state-of-the-art biostatistical analysis of clinical studies. Committee members will meet with Dr. Milush regularly to discuss results, progress, potential problems, and future directions. Furthermore, didactic courses, lectures, and research conferences have been carefully selected to provide Dr. Milush with additional training that will facilitate his transition to a completely independent investigator. The goal of this project is to develop a more detailed mechanistic understanding of neuroendocrine regulation of immune responses through the refinement and validation of novel flow cytometric assays for the assessment of glucocorticoid receptor expression and function (Aim 1). The novel assays will then be used to determine whether in vivo cortisol levels correlate with glucocorticoid receptor expression in immune cells (Aim 2). Lastly, these novel flow cytometry-based assays will be used to understand how mind-body interventions might 'reset' this important bi-directional communication between the neuroendocrine and immune system (Aim 3). This research will form the basis for a larger, more comprehensive investigation of the mechanisms by which mind-body intervention changes neuroendocrine signaling and immune system function in an R01 grant application before the end of the K award period. Public health relevance: A more complete understanding of neuroendocrine control of immune cell function is important for understanding the molecular mechanisms by which mind-body interventions affect immune function through modulation of neuroendocrine signaling. PUBLIC HEALTH RELEVANCE: Mind-body interventions, such as meditation and yoga, may have important effects on the immune system in part through the effects of these interventions on stress hormone signaling pathways. Our understanding of the potential effects of these interventions on the immune system is limited however, by gaps in our knowledge of how changes in stress hormone levels potentially achieved by these interventions actually affect the immune system. The long-term goal of this application is to develop new assays necessary to study the mechanisms by which stress hormones control immune cell function and how mind-body interventions 'reset' this communication pathway.